Avian reticuloendotheliosis virus (REV-T) is a replication-defective acute leukemia virus that transforms immature lymphocytes. REV-T stocks contain a replication-competent nontransforming helper virus (reticuloendotheliosis-associated virus: REV-A) which is present in 1000-fold excess. REV-A induces a suppressor cell population in the spleens of infected birds which can be detected within three days after virus infection. The suppressor cells prevent the proliferation of thymus-derived lymphocytes by a contract-mediated mechanism. We propose to define the mechanism by which REV-A induces this suppressor cell population. Replicating REV-A as well as other genetically related reticuloendotheliosis viruses induce this suppressor cell population suggesting that the induction of suppressor cells may be mediated by a viral precursor polypeptide. REV-T nonvirus producing transformed cells which do not contain viral precursor polypeptides but express a surface protein related to REV-A also induce suppressor cells. REV-A precursor polypeptides sharing sequences with the tumor cell antigen will be tested for their ability to induce suppressor cells. Experiments are also proposed to isolate the REV-A induced suppressor cells and characterize the interaction between the suppressor cells and immunoresponsive cells. Impairment of the cellular immune response is a general feature of the helper viruses of all known avian acute leukemia viruses. A number of experimental approaches will be employed to define whether helper-virus induced immunosuppression play a significant role in the pathogenesis of viral-induced leukemia. The role of the helper virus-induced immunosuppression on the tumorigenicity and invasive properties of REV-T transformed cells will be evaluated.